The student who interrupts Coulson before class with the comment "My homework's done. I swear. But then my dad... " is Clark Gregg's daughter, Stella Gregg.
Starting with this episode, the introductory sequence "Previously, on Marvel's Agents of S.H.I.E.L.D...." is no longer narrated by Clark Gregg, who plays Phil Coulson, but by Daisy Johnson actress, Chloe Bennett.
When Mace shows Coulson and Simmons the S.H.I.E.L.D. Wall of Valor, two of the first names appearing are "A. GUERTIN" and "G. KITSON," a reference to the Art Dept. Coordinator Aaron Guertin and the Writer of this episode George Kitson.
In the board room at the Triskelion, Fitz says "...we will make our society great again," echoing Trump's "Make America Great Again" slogan. This is another among many Trump references in this Season 4 arc.
Holden Radcliffe's island house in the Framework is the same house with the bell tower as Mr. Rourke's house on Fantasy Island (1977).